Reduced expression of E-cadherin in oral squamous cell carcinoma: relationship with DNA methylation of 5' CpG island.
E-cadherin, a Ca2+-dependent cell-cell adhesion molecule, is involved in the maintenance of the epithelial phenotype. The reduction of its expression is considered to be important in the invasive and metastatic potential of carcinomas. A series of 52 primary oral squamous-cell carcinomas (SCCs) were studied immunohistochemically for E-cadherin expression in microwave-treated paraffin-embedded sections using a monoclonal antibody (HECD-1). Significant correlation was found between reduced E-cadherin expression and tumor dedifferentiation, grade of invasiveness, and lymph node metastasis. The possibility of E-cadherin gene mutation was also investigated by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP), but none was found. In addition, to clarify the CpG methylation state around E-cadherin gene promoter in oral SCC, we examined DNA samples by PCR assay after restriction digestion with methylation-sensitive enzyme HpaII. CpG methylation was found in 9 (17%) of 52 primary oral SCCs, but not in the corresponding normal tissues. In particular, 8 of the 9 methylated cases showed reduced expression of E-cadherin and histologically diffuse invasion type of tumor. These results suggest that reduction of E-cadherin expression is associated with the progression of human oral SCCs, and CpG methylation of E-cadherin gene promoter causes reduction of E-cadherin expression in the tumor, resulting in acquisition of the invasive phenotype.
Saito
Y
Y
Department of Oral Surgery, School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba, 260, Japan.
Takazawa
H
H
Uzawa
K
K
Tanzawa
H
H
Sato
K
K
D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism; D018899:CpG Islands / Q000502:physiology*; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008969:Molecular Sequence Data; D009062:Mouth Neoplasms / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011401:Promoter Regions, Genetic; D018719:Erb-b2 Receptor Tyrosine Kinases
D015820:Cadherins; D004273:DNA, Neoplasm; D018719:Erb-b2 Receptor Tyrosine Kinases